This project involves a study of ACTH receptors in cell membranes from rat adrenal cells, and of the membrane bound hormonally sensitive adenylate cyclase. Hormone binding is measured with 125I-ACTH and adenylate cyclase activity by the conversion of 32P-ATP to 32P-cAMP. Both the hormone receptor and the cyclase can be solubilized with the aid of detergents. Goals of the present work are to define the structural requirements for ACTH binding, to develop effective ACTH antagonists, and to define the molecular mechanisms by which hormone binding leads to activation of the adenylate cyclase. BIBLIOGRAPHIC REFERENCES: Stowe, N.W. and D.A. Ontjes, Altered Responsiveness of Adenylate Cyclase to ACTH in Experimental Adrenal Hyperplasia, The Pharmacologist 18: 221 (1976) Abstract. Ways, D.K., C.F. Zimmerman, and D.A. Ontjes, Inhibition of ACTH Effects on Adrenal Cell Membranes by Synthetic ACTH Analogs: Correlation of Binding and Adenylate Cyclase Activation, Mol. Pharmacol. 12: 789-799 (1976).